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Decreased Hydroxylation of Steroid Hormones by Liver Microsomes from Rats Bearing Walker Carcinosarcoma 256¹

Department of Pharmacology, National Institute of Hygienic Sciences, Setagaya-ku, Tokyo, Japan

The hydroxylating activities of liver microsomes for progesterone and testosterone were markedly decreased in male and female rats bearing Walker carcinosarcoma 256. The decreases in the hydroxylating activities were greater in the male rats than in the female rats. The content of cytochrome P-450 in liver microsomes was decreased in the tumor-bearing male and female rats. Moreover, the binding capacity of P-450 with progesterone and testosterone was decreased in the liver microsomes from tumor-bearing male rats, but not in those from female rats. The administration of 17-methyltestosterone to the tumor-bearing male rats did not prevent the decrease in the binding capacity of P-450 or in the hydroxylating activities for progesterone and testosterone.

These results appear to correlate the decrease in the hydroxylating activities for steroid hormones in the male rats with the decrease in the content of P-450 and the binding capacity of P-450 with steroid hormones, while the decrease in the female rats is correlated with the decrease in the content of P-450. Since the binding capacity of P-450 for steroid hormones is regulated by androgen, these results suggest that the ability of androgen to cause an increase in the binding capacity of P-450 appears to be impaired in the tumor-bearing male rats.

¹ A preliminary account of the present study has been reported in Life Sci., 7 (Part II): 915, 1968.

² Present address: McArdle Laboratory for Cancer Research, University of Wisconsin, Madison, Wis. 53706.

Received 2/16/70. Accepted 5/20/70.